Project Summary/Abstract Deep brain stimulation (DBS) is a Food and Drug Administration (FDA) approved neurosurgical procedure that has emerged as the gold-standard treatment for drug-resistant Parkinson's disease (PD), the second most common neurodegenerative disorder, which affects more patients than the combined number of people diagnosed with multiple sclerosis, muscular dystrophy, and Lou Gehrig's disease. DBS is also used to treat refractory chronic pain, a debilitating condition that affects more than 100 million Americans. Despite the general effectiveness of DBS, its underlying mechanisms of action are still unclear. Uncertainties remain about which circuits are affected, which exact fiber bundles need to be targeted, and the most efficacious stimulation protocol. The meticulous use of neuroimaging, both for target verification and for monitoring treatment-induced changes in the functional connectivity of affected brain networks is an essential step in interpreting clinical outcomes, testing new hypotheses and, consequently, designing enhanced therapeutic protocols. In this regard, magnetic resonance imaging (MRI) appears excellently poised as a high-resolution, non-invasive imaging tool, which could help address these open questions. However, the interaction of the radiofrequency (RF) fields of MRI scanners and the implanted electrodes imposes serious safety hazards that restrict the applicability of MRI for DBS patients. As a result, available MRI methodologies for DBS patients are limited in resolution and suffer from severe image artifacts that confound studies of the functional connectivity of affected brain networks. This program develops and validates novel MRI methodologies tailored and validated for patient-specific geometries, which will bring MRI to bear on the clinical questions regarding the mechanism and targeting of DBS treatment. The specific aims of this project are, therefore: (1) to develop and validate a patient-adjustable, reconfigurable MRI transmit coil, integrated with a 32-channel close-fit brain array, which enables the reduction of the unwanted interaction of RF fields and implanted electrodes up to 100-fold below levels produced by currently available systems, while increasing the signal-to-noise ratio (SNR) up to four times at the level of cortical structures; (2) the validation of developed methodologies with comprehensive electromagnetic simulations and phantom experiments to determine the safe range of imaging parameters and optimize clinical imaging protocols; and (3) devising methodologies which use the developed technology to enhance prediction of altered patterns of functional connectivity of the cortico-striatal loops in advanced Parkinson's patients. The immediate goal of this project is to develop and optimize MRI methodologies to enhance structural and functional imaging of PD-affected brain networks at field intensities that are FDA approved for DBS imaging and to apply these methodologies for enhanced functional mapping of cortico-striatal loops in advanced PD patients. The outcome serves as the launching point for the long-term goal of enabling the study of dynamic DBS-induced changes in the functional architecture of the brain.